To clarify the role of autophagy in antibacterial host defense, we investigated the regulation mechanism of autophagy mediated by reactive persulfide species and protein S-guanylation, and effects of reactive persulfides produced by bacteria. S-Guanylation of bacteria in infected-host cells was found to be involved in bacterial killing by autophagy in host cells, and reactive persulfides produced by bacteria were suggested to suppress S-guanylation-mediated autophagy induction and contribute to its escape from defense mechanism of host cells.